The surfaces of teeth are in a constant balance between the loss and gain of minerals. This process is partially kept in balance by the chemical composition of saliva and the extra-cellular fluid. Disruption of the tooth surface integrity can occur by acidic food and beverages, bacterial challenge and erosion by exaggerated tooth brushing or grinding of the teeth.
These processes are accompanied by a demineralisation of the exposed tooth surfaces leading to clinical conditions such as dentine hypersensitivity and caries.
Enamel mainly consists of inorganic mineral substance (95% by weight=86% by volume). It does not consist of pure hydroxy apatite but of mixed apatite and defect apatite. In mixed apatite, calcium can be replaced by magnesium, strontium and other divalent cations. PO43− can be replaced by HPO42−, H2PO42−, CO32− or HCO3. In defect apatite, the location of calcium in the lattice remains empty.
In saliva, minerals like calcium and phosphates are dissolved. When pH drops in plaque and saliva, the dissolved phosphate ions are protonated and thus removed from the solution equilibrium. In order to re-establish the equilibrium, apatite crystals have to be dissolved from the enamel. Thus a demineralisation of the enamel (initial lesion) takes place. With raising pH, the reverse reaction occurs. Due to the over-saturation of the saliva with apatite, remineralisation takes place.
In an initial lesion immediately above the sound enamel, a translucent zone exists. It contains about 1% of pores. Sound enamel only contains about 0.1% of pores. These pores or micro-channels have a diameter of 0.5 to 1.5 μm and a depth of 100 μm, which eventually allow bacterial invasion.
Dentine or dentin is the tissue, situated beneath the enamel, that forms the major portion of a tooth. When challenged by demineralisation and bacteria, caries can result in enamel and dentine. Dentine hypersensitivity is a clinical condition defined by an exaggerated response of the pulpal nerve to stimuli like cold, sweet, etc. The basis of this condition is exposed dentine due to erosion of the enamel/cementum, due to gingival recession and/or periodontal surgery.
The mineral proportion of dentin represents only 70% by weight or 45% by volume. Dissolution of the dentin starts at a higher pH than the dissolution of enamel and it is much more porous. Therefore, caries spreads more rapidly upon reaching the dentin than in enamel. The body reacts with the formation of sclerosing dentin as an attempt to build a barrier between caries and pulp. Minerals are deposited in the tubules inhibiting the diffusion of acids, toxins and proteolytic enzymes as well as bacteria.
Many attempts have been made to treat dentine hypersensitivity. According to the prior art, one approach is to reduce the excitability of the pulp by changes of the chemical environment of the nerve. Therefore agents are used which make the tooth less sensitive. According to the prior art several nerve desensitising agents are known. For this purpose, predominantly potassium nitrate is used which is deployed in commercial toothpastes, for the desensitisation of teeth (U.S. Pat. Nos. 3,863,006, 4,009,327 and 4,751,072). In these patents, mainly formulation and compositions containing potassium salts, including potassium bicarbonate and potassium chloride, are described.
An additional attempt, according to the prior art, has been made to control dentine hypersensitivity by using agents obtunding the tubules partially or completely. These agents are described as tubule blocking agents. U.S. Pat. No. 4,990,327 discloses the desensitisation of teeth with strontium and fluoride ions. Furthermore, U.S. Pat. No. 3,888,976 discloses the treatment of sensitive teeth by using zinc and strontium ions. U.S. Pat. No. 5,211,937 discloses the use of charged polystyrene beads as a chemically inert agent which mechanically blocks the surface of tubules. U.S. Pat. Nos. 4,634,589 and 4,710,372 disclose the use of clays like laponite or hectorite to obtund the tubules. U.S. Pat. No. 5,270,031 discloses the use of polyacrylic acids with a typical molecular weight of approximately 450.000 to 4.000.000 used as tubule blocking agents. Furthermore, U.S. Pat. No. 4,362,713 discloses the use of water-soluble or water-swellable poly-electrolytes and their salts as tubule blocking agents.
Further, in the prior art, the use of substrates as spherical micro-particles is known, on which active therapeutic substances are adsorbed by chemical, electrostatic or ionic bonding, to accelerate the wound healing rate or bone regeneration. As a result, active chemical compounds can be released in a controlled way. These so-called micro-spheres can be hollow or massive; the chemical substance can be adsorbed on the surface or encapsulated within the sphere.
From U.S. Pat. No. 5,037,639, the use of amorphous, thus non-spherical calcium compounds is known, which are applied to the dentinal structure of the teeth reportedly leading to apatite formation in situ. This apatite formation reportedly leads to a remineralisation of the teeth and a reduction of hypersensitivity.
DE 695 24 747 T2 contains an extensive review of the prior art regarding the reduction of hypersensitivity with sub-micron particles and discloses the use of cationic charged colloidal particles in an aqueous environment. It is suggested, for example, to use commercially available non-spherical silica with an average particle size of 20 nm with a coating of aluminium oxide of 2 nm. This product consists of an aqueous, colloidal dispersion of the aluminium oxide-coated sub-micron particles. For dental compositions, the compound should be used on average in amounts of 0.1% to 10% by weight.
The thesis of Gerd Fischer entitled: “Development, Characterisation and Application of Novel Hybrid Materials” presented to the Faculty of Chemistry and Pharmaceutics of the Eberhard-Karls University of Tuebingen, 2004, describes the controlled synthesis of mono-disperse spherical silica particles with a diameter between 0.2 and 1.8 μm, according to the Sol-Gel-Process, and their combination with other materials. Among others, the coating and the co-condensation with hydroxyapatite, resulting in mono-disperse particles with diameters of between 1.5 and 3.5 μm is disclosed.
Within the combination, silica was used to generate shape and size whereas hydroxyapatite was used to introduce similarity to the dental material, for the restoration of enamel loss through the effect of the hydroxyapatite.
In EP 0 216 278 B1, the production of non-porous, mono-disperse spherical silica particles of the Sol-Gel Process, notably with a particle size of 0.05-10 μm is disclosed.
DE 103 30 204 A1 discloses a sol-gel-process for the preparation of non-porous, spherical, mono-disperse silica particles notably with a particle size between 0.2 and 1.2 μm, carrying molecules immobilised by so-called spacers at their surface.
Furthermore, WO 02/30380 A1 discloses the desensitisation of teeth by inducing a regeneration of bone materials to obtund the dentin tubules. Among others, the use of hydroxyapatite, fluoroapatite, chloroapatite, tricalcium phosphate and other substrates based on calcium phosphate is disclosed. These substances can be attached to a silica substrate with a particle size of the substrate <10 microns. The porous or non-porous particles carrying the desensitising agents are present in concentrations between 1% and 70% by weight in dental desensitising compositions like toothpaste, mouthwash, tooth powder, varnishes, chewing gum etc. The compositions may additionally contain typical ingredients like abrasives or additional desensitising or otherwise effective ingredients.
Disadvantageous, for all these agents for the desensitisation of teeth according to prior art, is that they only temporarily alleviate the symptoms without leading to a lasting obturation of open tubules by incorporation and remineralisation, i.e. crystal growth, since they are surface-acting only. Only a lasting occlusion of the tubules can prevent the occurrence of hypersensitive teeth.
These surface-acting substances according to the prior art are not able to achieve this. These substances penetrate the tubules insufficiently or not at all and cannot influence i.e. inhibit the nervous transmission. Because of the chemical structure of these substances they cannot be, or can only insufficiently be, incorporated into the existing tooth structure to generate a sufficient remineralisation of the teeth and an obturation of the tubules.
This not only applies for dentin but also for enamel. The prior art discloses a number of patents claiming remineralisation of enamel lesions and prevention of caries. U.S. Pat. No. 3,175,951 discloses, for instance, the use of fluorides to fight cavities.
In vitro and in vivo, it could be shown that initial lesions can be at least partly remineralised, and where applicable, even completely restored. Fluoride can influence the misbalanced interaction between de- and remineralisation in favour of remineralisation. Fluoride penetrates into the enamel by way of diffusion channels. In this way, fluoride is bound to the enamel forming fluoroapatite and fluoridated hydroxyapatite. In the outer layer of the enamel, less than 10% of the hydroxyl groups are replaced by fluoride, and in a depth of 50 μm, only 1% are replaced. While in saliva hydroxyapatite begins to be demineralised at a pH of 5.5. Fluoroapatite begins to demineralise in saliva at a pH of 4.6. Accordingly, in the presence of sufficient fluoride, remineralisation can begin to occur at a pH of 4.6 whilst without fluoride this occurs not until a pH 5.5.
Another method to promote remineralisation is the use of soluble calcium salts. U.S. Pat. No. 4,080,440 discloses the use of soluble calcium salts with soluble fluorides for the remineralisation of enamel. U.S. Pat. No. 4,048,300 discloses the use of calcium phosphates like fluoroapatite, fluorohydroxyapatite and hydroxyapatite as well as monofluorophosphate, carbonate and di-valent cations like zinc.
U.S. Pat. Nos. 6,733,818 and 6,846,500 combine amorphous calcium phosphate with casein-phosphopeptide and bicarbonate as chewing gums or confectionary. U.S. Pat. Nos. 5,858,333 and 5,603,922 disclose the use of products in dual chamber tubes, one chamber containing soluble calcium salts and the other chamber containing phosphates and fluoride, mixing upon simultaneous squeezing from the tube and leading to remineralisation in situ. U.S. Pat. Nos. 5,534,244, 5,437,857 and 5,460,803 disclose the use of amorphous strontium and calcium phosphates with or without fluoride for remineralisation of enamel. U.S. Pat. No. 6,521,215 discloses compositions and methods for bleaching and remineralisation of teeth, for treating hypersensitive teeth and for the treatment of caries, with a soluble calcium phosphate consisting of one or more compounds of the group monocalcium phosphate, tricalcium phosphate and tetracalcium phosphate. U.S. Pat. No. 4,923,683 discloses the use of micro-encapsulated hydroxyapatite and/or fluoride.